Relation between soluble adhesion molecules and insulin sensitivity in type 2 diabetic individuals: role of adipose tissue.

OBJECTIVE: The purpose of this study was to explore the relation between insulin resistance and plasma levels of soluble adhesion molecules and to examine the effects of acute hyperinsulinemia on these molecules in type 2 diabetic individuals. RESEARCH DESIGN AND METHODS: Intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E- and P-selectin plasma concentrations were measured in 36 nonobese type 2 diabetic patients without cardiovascular disease and in 7 healthy subjects. Insulin sensitivity was assessed by a 4-h euglycemic ( approximately 5 mmol/l)-hyperinsulinemic ( approximately 300 pmol/l) clamp performed in combination with [(3)H]3-D-glucose infusion. RESULTS: Diabetic subjects were insulin resistant but did not show plasma concentrations of adhesion molecules that were significantly higher than control subjects. In diabetic subjects, plasma ICAM-1 and E-selectin were negatively correlated with total glucose disposal during the insulin clamp (r = -0.432, P < 0.01; and r = -0.375, P < 0.05, respectively), whereas plasma VCAM-1 and P-selectin were not. Plasma ICAM-1 as well as E- and P-selectin were positively correlated with BMI, total body fat (TBF), and waist girth (P < 0.05-0.001). In multiple regression analyses, the relation of plasma ICAM-1 and E-selectin with insulin sensitivity was lost after adjustment for potential confounders, including HbA(1c), blood pressure, and/or LDL cholesterol. In these analyses, BMI was the only independent predictor of plasma ICAM-1 (R(2) = 0.244, P < 0.002), whereas TBF was the only independent predictor of plasma E-selectin (R(2) = 0.202, P = 0.01). The 4-h insulin infusion during the glucose clamp did not significantly change plasma levels of adhesion molecules. CONCLUSIONS: Overall adiposity, rather than insulin resistance, may be a determinant of plasma levels of ICAM-1 and E-selectin in type 2 diabetic individuals. In these patients, acute hyperinsulinemia does not exert any significant effect on plasma adhesion molecules. These findings support the possibility that adipose tissue releases one or more factors that may adversely affect endothelial function on one hand and insulin sensitivity on the other.